Denise H. Frank is a junior investigator newly involved in cancer prevention research at the University of Arizona, Arizona Cancer Center (AZCC). Dr. Frank has recently completed a cancer prevention supplement award to reenter biomedical science after a career hiatus. By expanding her research skills in image analysis and spatial analytical techniques, she has begun to forge a new career. Her reentry represents a major shift from vector-borne infectious disease prevention to cancer prevention research. This proposal requests five years of funding for Dr. Frank for significant and comprehensive mentored research training in cancer prevention. The career development award will provide her with continued mentoring and formal training to successfully build on the foundation achieved through the supplement award, culminating in a career as an independent researcher/translational scientist in cancer prevention. She seeks to 1) significantly update her analytical and theory-based knowledge, especially as it pertains to the role of karyometric analysis for early changes in breast tissue that signal increased risk, and chemoprevention through didactic training and 2) gain needed, additional experience in clinical trial research. Specifically, Dr. Frank proposes to gain knowledge in advanced molecular technologies to augment her skills in biomarker evaluation, and update her biostatistical knowledge with interdisciplinary training in advanced analytical and multivariate approaches. Together, these training opportunities will enable her to analyze complex image patterns. Dr. Frank's training will occur primarily at the University of Arizona and the AZCC, with some activities based at NIH and other extramural workshop locations. The University of Arizona is a top ranked research university. The AZCC is an NCI designated comprehensive cancer center with an international reputation in cancer prevention research. Dr. Frank's mentor, Dr. David S. Alberts, is internationally known for his expertise in cancer prevention and has a long established record of mentoring junior scientists toward their own successful independent research careers. Dr. Frank's research goals are to evaluate quantitative karyometry as a biomarker of nuclear abnormalities that signify increased risk of developing breast cancer and to assess chemopreventive efficacy. Pilot data based on quantitative karyometry show significant sub-visual cytologic changes in normal appearing cell nuclei among defined risk categories. She proposes to 1. expand these very promising data in a prospective trial which aims to more accurately characterize abnormalities across a range of diagnostic categories and 2. conduct a retrospective study of karyometric changes in breast nuclei pre and post chemopreventive agent intervention. The proposed research directly addresses unmet clinical needs to more accurately assess individual cancer risk and response to chemoprevention to reduce the burden of cancer.